1-74216284-A-G

Variant names:

• chr1-74216284-A-G
• rs792321
• ENST00000557284.7:c.343+14874A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001112808.3(FPGT-TNNI3K):​c.343+14874A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,502 control chromosomes in the GnomAD database, including 14,311 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (14311 hom., cov: 32)
• Consequence: FPGT-TNNI3K NM_001112808.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 12 publications found

Genes affected

FPGT-TNNI3K (HGNC:42952): (FPGT-TNNI3K readthrough) Enables protein C-terminus binding activity; protein kinase activity; and troponin I binding activity. Involved in protein phosphorylation and regulation of heart contraction. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FPGT (HGNC:3825): (fucose-1-phosphate guanylyltransferase) L-fucose is a key sugar in glycoproteins and other complex carbohydrates since it may be involved in many of the functional roles of these macromolecules, such as in cell-cell recognition. The fucosyl donor for these fucosylated oligosaccharides is GDP-beta-L-fucose. There are two alternate pathways for the biosynthesis of GDP-fucose; the major pathway converts GDP-alpha-D-mannose to GDP-beta-L-fucose. The protein encoded by this gene participates in an alternate pathway that is present in certain mammalian tissues, such as liver and kidney, and appears to function as a salvage pathway to reutilize L-fucose arising from the turnover of glycoproteins and glycolipids. This pathway involves the phosphorylation of L-fucose to form beta-L-fucose-1-phosphate, and then condensation of the beta-L-fucose-1-phosphate with GTP by fucose-1-phosphate guanylyltransferase to form GDP-beta-L-fucose. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream TNNI3 interacting kinase (TNNI3K) gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001112808.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPGT-TNNI3K	NM_001112808.3		c.343+14874A>G		intron	N/A	NP_001106279.3
	FPGT-TNNI3K	NM_001199327.2		c.343+14874A>G		intron	N/A	NP_001186256.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPGT-TNNI3K	ENST00000557284.7	TSL:2	c.343+14874A>G		intron	N/A	ENSP00000450895.3
	FPGT-TNNI3K	ENST00000370899.7	TSL:2	c.343+14874A>G		intron	N/A	ENSP00000359936.3
	FPGT-TNNI3K	ENST00000370895.5	TSL:2	c.343+14874A>G		intron	N/A	ENSP00000359932.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62525 AN: 151384 Hom.: 14318 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.405

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.413 AC: 62521 AN: 151502 Hom.: 14311 Cov.: 32 AF XY: 0.418 AC XY: 30946 AN XY: 74044

African (AFR) AF: 0.212 AC: 8767 AN: 41386

American (AMR) AF: 0.424 AC: 6425 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1946 AN: 3458

East Asian (EAS) AF: 0.729 AC: 3732 AN: 5122

South Asian (SAS) AF: 0.544 AC: 2620 AN: 4814

European-Finnish (FIN) AF: 0.500 AC: 5271 AN: 10550

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.476 AC: 32205 AN: 67708

Other (OTH) AF: 0.407 AC: 855 AN: 2102

Alfa AF: 0.420 Hom.: 2278

Bravo AF: 0.400

Asia WGS AF: 0.543 AC: 1891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.94
DANN	Benign	0.44
PhyloP100		-0.052
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs792321; hg19: chr1-74681968; COSMIC: COSV63846410;